112667-29-5

Upstream product

• 35661-40-6 N-Fmoc L-Phe 
• 103321-57-9 2S-flouren-9-ylmethoxycarbonylamino-3-phenylpropionyl chloride 
• 497-19-8 sodium carbonate 
• 683218-30-6 N-(9-fluorenylmethyloxycarbonyl)-3-amino-3-(4,5-dimethoxy-2-nitrophenyl)propionic acid 
• 84890-98-2 Fmoc-Phe-O-COO-isoBu 

Downstream Products

• 1017241-08-5 5'-(6-aminohexyl)-TTTTT-3' 
• 1159182-96-3 5'-(6-Phe-aminohexyl)-TTTTT-3' 
• 5241-58-7 L-Phenylalanine amide 
• 1427289-32-4 C₃₄H₃₂N₃O₈P 
• 1456856-71-5 NapFFGGG 
• 1456856-74-8 C₄₅H₅₃N₁₁O₆ 
• 1456856-70-4 C₃₉H₄₀N₆O₆ 

Relevant academic research and scientific papers

Identification of Pyridine Synthase Recognition Sequences Allows a Modular Solid-Phase Route to Thiopeptide Variants

Thiopeptides are structurally complex, bioactive natural products derived from ribosomally synthesized and post-translationally modified peptides. A remarkable set of enzymes were recently revealed to catalyze the formation of the core trithiazolylpyridine of thiopeptides via a formal [4 + 2] cycloaddition. These pyridine synthases typically act late in thiopeptide biosynthesis to affect macrocyclization and cleavage of the N-terminal leader peptide, making them potentially useful biocatalysts for preparation of new thiopeptide variants. Herein we investigate the leader peptide requirements for TclM from thiocillin biosynthesis in Bacillus cereus ATCC 14579. Through a series of truncations, we define a minimum recognition sequence (RS) that is necessary and sufficient for TclM activity. This RS can be readily synthesized and ligated to linear thiopeptide cores prepared via solid-phase peptide synthesis (SPPS), giving an efficient and modular route to thiopeptide variants. We exploit this strategy to define C-terminal core peptide requirements and explore the differences in promiscuity of two pyridine synthases, TclM and TbtD, ultimately examining their ability to access new structural variants.

Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine

Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.

Efficient Route to Deuterated Aromatics by the Deamination of Anilines

One-step replacement of NH2 groups in ring-substituted anilines by deuterium is reported. Approaches comprising both solid-phase and solution-phase syntheses can be used on a large variety of substrates. The method uses diazotization in a mixture of water and either dichloromethane or chloroform, which serve as a source of hydrogen. This protocol can be used as a general method for fast and easy incorporation of deuterium into an aromatic system using deuterated chloroform.

One-pot synthesis of orthogonally protected dipeptide selenazoles employing Nα-amino selenocarboxamides and α-bromomethyl ketones

A simple and efficient protocol for the synthesis of selenazole containing dipeptidomimetics using Nα-amino selenocarboxamides and α-bromomethyl ketones is described. All the compounds made were isolated in good yields and fully characterized.

Unexpected hydrolytic instability of N-acylated amino acid amides and peptides

Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent's Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis.

Convenient preparation of primary amides via activation of carboxylic acids with ethyl chloroformate and triethylamine under mild conditions

Primary amides were easily prepared in 22-99% yields from the corresponding carboxylic acids 1 or 5 with NH4Cl via activation with ClCO 2Et and Et3N. The enantiomers of the corresponding primary amides of Cbz-, Boc-, or Fmoc-α-amino acids can be separated by using a chiral column.

Facile synthesis of N-(9-fluorenylmethyloxycarbonyl)-3-amino-3-(4,5- dimethoxy-2-nitrophenyl)propionic acid as a photocleavable linker for solid-phase peptide synthesis

A photocleavable linker, N-(9-fluorenylmethyloxycarbonyl)-3-amino-3-(4,5- dimethoxy-2-nitrophenyl)propionic acid was synthesized from veratraldehyde, with simple reaction and separation steps. This linker was stable under the normal solid-phase peptide sy

Development and evaluation of novel phosphotyrosine mimetic inhibitors targeting the Src homology 2 domain of signaling lymphocytic activation molecule (SLAM) associated protein

Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have incorporated a novel phosphotyrosine mimetic, which is an unusual amino acid carrying a cyclosaligenyl (cycloSal) phosphodiester moiety, into dipeptides to investigate the inhibitory effect on SH2 domain-containing proteins. A plate-based assay was also established to screen for inhibitors that disrupt the interaction between a phosphopeptide of SLAM (signaling lymphocytic activation molecule) and its interacting protein SAP (SLAM-associated protein). We identified a number of inhibitors with IC50 values in the range of 17-35 μM, implying that the cycloSal phosphodiester-carrying amino acid could mimic the phosphotyrosyl residue. Our results also raise the possibility of integrating the newly developed phosphotyrosine mimetic moiety into inhibitors designed for other SH2 domain-containing proteins.

A novel approach to the solid-phase synthesis of peptides with a tetrazole at the C-terminus

Peptidomimetics containing a C-terminal tetrazole can be easily prepared using modifications to traditional peptide synthesis protocols. Georg Thieme Verlag Stuttgart.